This invention relates to a novel process for preparing 9-(2,6-dihalobenzyl)adenines. Said purines are described in U.S. Pat. No. 3,846,426 as being useful in the treatment and prevention of coccidoisis.
Coccidiosis is a widespread poultry disease which is produced by infections of protozoa of the genus Eimeria which causes severe pathology in the intestines and ceca of poultry. Some of the most significant of these species are E. tenella, E. acervulina, E. necatrix, E. brunetti and E. maxima. This disease is generally spread by the birds picking up the infectious organism in droppings on contaminated litter or ground, or by way of food drinking water. The disease is manifested by hemorrhage, accumulation of blood in the ceca, passage of blood in the droppings, weakness and digestive disturbances. The disease often terminates in the death of the animal, but the fowl which survive severe infections have had their market value substantially reduced as a result of the infection. Coccidiosis is, therefore, a disease of great economic importance and extensive work has been done to find new and improved methods for controlling and treating coccidial infections in poultry.
9-(Dihalobenzyl)adenines have been prepared by alkylating adenine with dihalobenzyl halides. This process suffers from the disadvantage that alkylation is not selective and substitution occurs to some extent at the 3-position and other positions of adenine.
E. C. Taylor, et al., J. Org. Chem. 36, 3211 (1971) have reported that 9-substituted adenines (2) may be prepared via reductive cleavage and subsequent cyclization of 7-amidofurazano[3,4-d]pyrimidines (1). ##STR1## Although a wide variety of adenine derivatives was prepared, the authors were unable to effect the conversion of 5-unsubstituted 7-amidofurazano[3,4-d]pyrimidines (1, R=H, Y=O) to 2-unsubstituted adenines (2, R=H) due to the hydrolytic instability of the former compounds.
According to the process of the present invention this conversion has been successfully performed in the case wherein in compound (1) R=H, Y=S and R'= dihalobenzyl to provide 9-(dihalobenzyl)adenines (2) wherein R=H and R'= dihalobenzyl uncontaminated with positional isomers.